Cancer Genetics and Cytogenetics 157 (2005) 148–150

Short communication

Primary myeloid sarcoma of the testicle with t(15;17)Shanti Gopal, Sandra Marcussen, Sheila M. Dobin, William Koss, Ludvik R. Donner*

Department of Pathology, Scott and White Memorial Hospital and Clinic; Scott, Sherwood and Brindley Foundation;The Texas A&M University Health Science Center College of Medicine, 2401 South 31st Street, Temple, TX 76508

Received 10 May 2004; received in revised form 4 June 2004; accepted 11 June 2004

Abstract The first case of acute promyelocytic leukemia presenting as a solitary testicular mass (myeloidsarcoma) that relapsed in the contralateral testicle is described. The neoplastic cells stronglyexpressed chloroacetate esterase, myeloperoxidase, CD33, CD43, and weakly, CD117. The presenceof many azurophil granules and Auer rods was detected by electron microscopy. Translocation(15;17)(q22;q21.1) was revealed by cytogenetics and was verified by fluorescence in situ hybridiza-tion. Contralateral testicle is a favorite site for recurrence in a subset of testicular myeloid sarcomas.Subclassification of all cases of myeloid sarcoma ought to be attempted. � 2005 Elsevier Inc. Allrights reserved.

1. Introduction

Primary myeloid (granulocytic) sarcomas of the testicleare rare tumors and only a handful of them have beenreported [1–8]. The majority of these tumors were neitherfurther subclassified nor studied by cytogenetics or molecu-lar biology, except for 2 tumors that were retrospectivelyclassified as acute myelomonocytic [2] and acute mono-blastic leukemias [5], respectively.

Acute promyelocytic leukemia (APL) is defined by thet(15;17)(q22;q21.1) or by its variants. The t(15;17) leads tofusion of the retinoic acid receptor α (RARa) gene on17q21.1 with a nuclear regulatory factor PML gene on 15q22.The PML gene functions as a tumor suppressor and lossof its function in the leukemic cells renders them less respon-sive to differentiation stimuli, like retinoic acid, and conferson them a proliferative advantage [9,10]. Because dissemin-ated intravascular coagulation occurs in the majority of pa-tients, rapid diagnosis of this leukemia and early retinoicacid treatment are essential [11]. The first case of acutepromyelocytic leukemia presenting as a solitary testicularmass is presented in this article.

2. Clinical history

A 27-year-old black man presented with a large, painlessmass in the left testicle. Radical orchiectomy was performed.

* Corresponding author. Tel.: (254) 724-4730; fax: (254) 724-4391.E-mail address: ldonner@swmail.sw.org (L.R. Donner).

0165-4608/05/$ – see front matter � 2005 Elsevier Inc. All rights reserved.doi:10.1016/j.cancergencyto.2004.06.010

The bone marrow and peripheral blood, abdominal sono-gram, computed tomogram of the abdomen, pelvis, and thechest were all normal. The mass was classified as myeloidsarcoma. No further treatment was administered. The patientdid well for a year but subsequently developed a mass inthe contralateral testicle. A right radical orchiectomy wasperformed. The recurrent myeloid sarcoma was subclassifiedas APL and the patient treated with trans-retinoic acid, daun-orubicin, and cytosine-arabinoside. A bone marrow biopsywas performed four months later. The bone marrow wasmildly hypercellular, had diploid karyotype, but 1% of theinterphase cells had a rearranged RARa gene at band 17q21.1that was detected by fluorescence in situ hybridization(FISH).

3. Pathology study

The left and right testicles contained a 4.5 × 4.0 × 3.0cm and 6.0 × 4.5 × 4.0 cm firm solid green tumors, respec-tively (Fig. 1A). A 1.4-cm similar tumor was also found onthe outer surface of the right spermatic cord. The parenchymaof both testicles was replaced by sheets of neoplastic cellsthat were entrapping atrophic seminiferous tubules. Theirnuclei were bilobed or reniform with fine chromatin, smallnucleoli and granular cytoplasm (Fig. 1B and C). A thirdof the neoplastic cells were strongly chloroacetate esterasepositive. They were strongly diffusely positive for myeloper-oxidase and CD43, weakly positive for CD117, and negativefor CD34 when studied by immunohistochemistry (Fig. 1D);positive for CD33 and CD117, and negative for CD13 and

S. Gopal et al. / Cancer Genetics and Cytogenetics 157 (2005) 148–150 149

Fig. 1. (A) Gross appearance of the recurrent testicular tumor; (B) lightmicroscopy, plastic embedded; (C) light microscopy, H&E; and (D) immu-noreactivity for myeloperoxidase.

HLA-DR when studied by flow cytometry. A subset of thecells was positive for CD34 when studied by the lattermethod. Numerous azurophil granules and many Auer rodswere detected in the right testicular tumor by electron mi-croscopy (Fig. 2).

4. Cytogenetic study

Six cell cultures were established from the right testicularmass, 2 from explants and 4 from collagenase-treated cells.

Fig. 2. Ultrastructure of the recurrent tumor. Note the presence of numerousazurophilic granules and Auer rods.

Cultures were harvested 1–8 days later. Twenty-one GTG-banded mitotic figures were analyzed. All 6 cultures con-tained a clonal population with the karyotype 46,XY,t(15;17)(q22;q21.1)[18].nuc ish 17q21.1(5′RARAx2,3′RARAx2)(5′RARAsep 3′RARAx1)[178]/46,idem,del(1)(p32p36.2)[2]/46,XY[1].nuc ish 17q21.1(5′RARAx2,3′RARAx2)[21] (Fig. 3). Therearrangement of the RARa gene on 17q21.1 was verifiedwith the LSI RARA dual-color probe (Vysis, Downer Grove,IL) (Fig. 4).

5. Discussion

This case reiterates the importance of subclassification ofmyeloid sarcomas for their optimal therapeutic management.

Fig. 3. Karyotype of the recurrent tumor. The abnormal chromosomes are marked by arrows.

S. Gopal et al. / Cancer Genetics and Cytogenetics 157 (2005) 148–150150

Fig. 4. Fluorescence in situ hybridization (FISH) using the retinoic acidreceptor gene probe. Note split of the signals in the recurrent tumor (3′end labeled green, 5′ end labeled red).

Patients with APL benefit from treatment with retinoids orarsenic compounds [12,13]. The microgranular variant ofthis leukemia can be diagnostically difficult because themorphologic, cytochemical, and immunophenotypic fea-tures are often non-specific [14,15]. The chromosomal trans-locations in APL include, the classic t(15;17)(q22;q21.1)and at least 3 variants, the t(11;17)(q23;q21) in which theRARa gene fuses with the promyelocytic leukemia zincfinger gene PLZF on 11q23, the t(11;17)(q13;q21) in whichthe nuclear matrix associated gene (NuMA) on 11q13 fuseswith the RARa gene, and the t(5;17)(q35;q21), in which thenucleophosmin (NPM) gene on 5q35 fuses with the RARagene [9].

The recurrence of the tumor in the contralateral testiclerepresents a clinically interesting aspect of this case. Similarrecurrences have occurred in the 2 previously reported cases[1,2] indicating that the testicle is a site of likely recurrencein a subset of these tumors.

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